The long range objective of this project is to elucidate the basic mechanisms of drug allergy in man, and to apply current and new knowledge to the development of diagnostic methods and therapeutic approaches to the clinical problems which drug hypersensitivity pose. The general approach is to develop a reliable in vitro assay which would be diagnostic of drug hypersensitivity states. This assay will then be utilized to study the immune response to drugs in man with the general aim of pinpointing the variables which contribute to the development of a hypersensitive status. The model system chosen for study is the most prevalent drug allergy, penicillin hypersensitivity. Our previous work supports the usefulness of skin testing with penicillin derivatives in predicting reaction to the drug, suggesting that reaginic (IgE) antibodies play a primary role in the pathogenesis of these reactions. We now propose to apply the radioallergoabsorbent technique (RAST), which allows the measurement of allergen-specific IgE antibodies in human serum, to the development of an in vitro assay for penicillin allergy. The performance of this in viiro serum assay is then to be compared with direct skin testing in an extended clinical trial. The availability of an in vitro assay for drug allergy will allow us to proceed to studies of the immune response to drugs in man with greater safety and ease. Serial serum specimens will be assayed for IgE anti-drug antibodies in a series of inpatients receiving penicillin therapeutically. Study protocols will investigate the influence of immunologic status; dose, route and duration of therapy, and physiological variables on the induction of anti-penicillin reagins.